Medical pressure-sensitive adhesives with high permeability to water vapor and high adhesive force, and plasters provided therewith

ABSTRACT

Medicinal pressure-sensitive adhesives, adhering to both dry and wet skin, characterized by a mixture of 
     a) 20-50 wt-% of a hydrophilic (meth)acrylate copolymerizate containing tertiary amino groups, 
     b) 20-50 wt-% of a hydrophobic (meth)acrylate copolymerizate containing carboxyl groups, 
     c) 10-40 wt-% of one or more mono- or dicarboxylic acids, 
     d) 0-10 wt-% of a polyol, and 
     e) 0.02-0.5 wt-% of a cross-linking system reacting with at least one copolymerizate, 
     whereby the sum of components a to e equals 100 wt-%, with a water-vapor permeability of ≧30,000 g·m −2 ·24 h −1 , measured on a pressure-sensitive adhesive film with a thickness of 40 μm.

The invention relates to medicinal pressure-sensitive adhesives whichadhere to both dry and wet skin, and to plasters provided with saidadhesives.

The present invention especially relates to medicinal pressure-sensitiveadhesives with excellent adhesion and with a water-vapor permeability(WVP) of at least 30,000 g·m⁻²·24 h⁻¹ (measured on a pressure-sensitiveadhesive film with a weight of 40 g/m²) and to their use for theproduction of pressure-sensitive adhesive medical products, e.g. foremergency or sports medicine.

The term pressure-sensitive adhesive here denominates adhesives whichadhere reversibly to the respective surface through exertion ofpressure.

The water-vapor permeability is the amount of water which escapes froman inverted cup—sealed with the substrate and filled with water—throughthe substrate to be measured per area and time at an ambient climate of40° C. and 20% relative humidity.

DE-OS 44 16 928 teaches wet adhesives on the basis of acrylatecopolymers. Further components are emulsifiers containing quaternaryammonium groups, emulsifiers containing polyoxyalkylenes, polyvinylcarboxylic acid, tackifying resins and cross-linking agents. Thedisadvantages of the products manufactured according to this documentare on the one hand that the adhesives only adhere well to moist skin ifthe skin is dried before application, and on the other hand that theemulsifiers containing quaternary ammonium groups are not cross-linkedwith the polymer backbone, so that they can be dissolved out in dampsurroundings and have a cytotoxic effect. Also, the water-vaporpermeability of 30,000 g·m⁻²·24 h⁻¹ described in said document, measuredon a pressure-sensitive adhesive film with a weight of 30 g/m², is inmany cases insufficient.

EP 0 415 055 describes pressure-sensitive adhesives with thewater-soluble salt of an uncrosslinked copolymer of an aminogroup-containing monomer and at least one alkyl(meth)acrylate.

The disadvantages of this adhesive are on the one hand that the adhesivecharacteristics of the thus produced adhesive depend very strongly onthe residual moisture content, thus making a complicated controlling ofthe drying conditions necessary, and on the other hand that the adhesivehas absorbed so much moisture after a longer wearing period that whenthe carrier material is pulled off of the skin, the adhesive completelyremains on the skin and must be removed with much effort using a soapsolution.

It is thus the object of the present invention to provide medicinalpressure-sensitive adhesives which adhere excellently to dry, moist andwet skin and at the same time avoid the above mentioned disadvantagessuch as the necessity of pre-drying the skin, cytotoxic components andadhesive residue upon removal, and which are also suited for longerwearing periods due to their high WVP of at least 30,000 g·m⁻²·24 h⁻¹30,000 g·m⁻²·24 h⁻¹, at a pressure-sensitive adhesive film weight of 40g/m².

These surprisingly good characteristics are achieved in the adhesiveaccording to the present invention which is characterized by a mixtureof

a) 20-50 wt-% of a hydrophilic (meth)acrylate copolymerizate containingtertiary amino groups,

b) 20-50 wt-% of a hydrophobic (meth)acrylate copolymerizate containingcarboxyl groups,

c) 10-40 wt-% of one or more mono- or dicarboxylic acids,

d) 0-10 wt-% of a polyol, and

e) 0.02-0.5 wt-% of a cross-linking system reacting with at least onecopolymerizate,

whereby the sum of components a to e equals 100 wt-%, with a water-vaporpermeability of ≧30,000 g·m⁻²·24 h⁻¹, measured on a pressure-sensitiveadhesive film with a thickness of 40 μm.

The pressure-sensitive adhesive according to the invention adheresexcellently to both dry and sweaty skin, it can be removed from the skinwithout residue, and it has such a high WVP that it enables a longerwearing period even in damp surroundings.

Eudragit® E 100 (Röhm Pharma) is an example for a hydrophilicmethacrylate copolymerizate containing tertiary amino groups.

Durotak® 1050 (National Starch & Chemical) is an example for ahydrophobic acrylate copolymer containing carboxyl groups. Suitablecarboxylic acids are lauric, myristic or palmitic acid, and suitabledicarboxylic acids are adipic, octanedioic or sebacic acid.

Glycerin is a polyol according to the invention.

Cross-linking agents are e.g. metal chelates, metal acid esters,polyisocyanates, epoxide resins, aziridine resins, and triazine resins.

A further object of the invention is the use of the pressure-sensitiveadhesives according to the invention for the production ofpressure-sensitive adhesive medical products e.g. for emergency,intensive care and sports medicine, and also for occlusive dressingssuch as e.g. transdermal systems. If necessary, the medical products canbe sterilized by water vapor, y-irradiation or gassing with ethyleneoxide.

The thus obtained pressure-sensitive adhesives were evaluated—coatedonto polyurethane films with good breathing properties—by means ofphysical-technical tests such as WVP (the water-vapor permeability ofthe pressure-sensitive adhesive film is calculated according to thefollowing formula:$\frac{1}{{WVP}_{total}} = {\frac{1}{{WVP}_{{polyurethane}\quad {film}}} + \frac{1}{\left. {WVP}_{adhesive} \right)}}$

and testing of the adhesive strength on steel plates according to AFERA4001 as well on a skin model of polyurethane. With this skin model, anadhesive strength is achieved which is, on average, approximately 2N/25mm higher than the corresponding average value on human skin. This isvalid basically regardless of whether the pressure-sensitive adhesive isbased on natural or synthetic rubber, a solvent- or water-based acrylatecopolymer, or a silicon.

The samples were further tested on the skin of twenty test personsfollowing a given evaluation system by means of statistical analysis.Strips of 2.5 cm×5 cm were applied to the hairless inner section of theforearms (dry), and pieces of 3 cm×3 cm were applied to the freshlywashed and dried (moist) and undried (wet) palms of the test persons.Apart from the subjective evaluation of the adhesive strength after 1hour and after 24 hours, further evaluation criteria were thedermatological acceptability and a pain-free, residue-free removal. Thestatistical analysis of these tests, whereby a standard was always setat 100%, led to the result that products with the pressure-sensitiveadhesives according to the invention adhere to dry and wet skin withoutproblem, do not cause skin irritations, and can be removed practicallywithout residue.

In the following, the present invention is described in more detail withthe help of the following examples:

EXAMPLE 1

200 g of ethyl acetate are placed into a 1 l reaction vessel with astirrer, drip funnel, reflux cooler and gas supply nozzles, and heatedto 80° C. Within a time span of 50 minutes, a monomer mixture of 80 g ofn-butyl acrylate, 80 g of ADAME (Elf Atochem), 40 g of methacrylic acid,and 0.5 g of VAZO 64 (Du Pont) is added dropwise under stirring. After afurther 6 hours and cooling to 60° C., 60 g of ethyl acetate and 40 g ofisopropanol, together with 120 g of lauric acid and 22 g of adipic acid,are added to this copolymerizate A. After cooling to room temperature,20 g of glycerin and 340 g of a copolymerizate B, polymerized asdescribed above from 200 g of n-butyl acrylate, 275 g of 2-ethylhexylacrylate, 25 g of acrylic acid, and 2.5 g of VAZO 64 in 500 g of ethylacetate, are admixed to the homogenous mixture. Furthermore, 100 g of a2.5% aluminum acetylacetonate (AlAcA) solution are added forcross-linking.

The thus obtained pressure-sensitive adhesive is coated onto asiliconized polyester film in different layer thicknesses with aspreading knife and dried for 30 minutes at 80° C. in a vent air dryingcabinet, resulting in pressure-sensitive adhesive films with a thicknessof 25 μm, 45 μm and 60 μm (referred to as a, b and c). Thepressure-sensitive adhesive films are transfer laminated onto apolyurethane film with a thickness of 25 μm and a WVP of 40,000 g·m⁻²·24h⁻¹. The evaluation (see Table 1) was carried out in comparison to astandard commercial product composed of a pressure-sensitive adhesivefilm with a thickness of 30 μm and a polyurethane film with a thicknessof 25 μm.

TABLE 1 Unit Standard a) b) c) Thickness of the μm 25 25 25 25polyurethane film Thickness of the μm 30 25 45 60 adhesive filmWVP_(pressure-sensitive) g · m⁻² · 5000 62100 49300 38400_(adhesive film, inverted cup) 24 h⁻¹ Adhesive strength N/25 mm 7.5 4.05.2 6.1 AFERA 4001 Adhesive strength N/25 mm 3.6 6.2 6.5 6.9polyurethane skin model subjective evalu- ation, normed at a standard of100% dry % 100.0 99.8 102.9 105.2 moist % 100.0 130.2 153.0 142.8 wet %100.0*¹ 180.2 210.7 254.8 *¹: very weak adhesion or no adhesion at all

In comparison with the standard, an almost equal level of adhesivestrength can be observed in the measurement on dry skin (under normalambient conditions).

In the measurement on moist skin and especially on wet skin, theexcellent performance of the new pressure-sensitive adhesive becomesapparent. Whereas the standard product does not adhere to the wet skinof most of the test persons, the pressure-sensitive adhesive accordingto the invention continues to achieve a sufficient adhesive strength.

EXAMPLES 2-5

The following mixtures were processed analogously to Example 1 (thegiven values apply to the respective solid materials) and coated so asto achieve a pressure-sensitive adhesive film of the determinedthickness:

Example 2 Example 3 Example 4 Example 5 hydrophilic 240 g of 140 g of186 g of 183 g of copolymer copolymer A copolymer A Eudragit Eudragit E100 E 100 (Röhm (Röhm Pharma) Pharma) hydrophobic 127 g of 140 g of 167g of 211 g of copolymer copolymer B Durotak copolymer B Durotak 10501050 (National (National Starch) Starch) fatty acid 99 g of 140 g of 112g of 183 g of lauric acid myristic lauric acid myristic acid aciddicarboxylic 17 g of 35 g of 20 g of 14 g of acid octanedioic sebacicacid adipic acid octanedioic acid acid polyol 14 g of 14 g of 13 g of —glycerin glycerin glycerin crosslinking 2.1 g of 0.7 g of 1.5 g of 1.4 gof agent A1AcA A1AcA CX-100*¹ PBT*² solid 35% 40% 50% 40% material *¹:aziridine resin (ICI); *²: polybutyl titanate

The analogous evaluation led to the following values:

Exam- Exam- Exam- Exam- Unit ple 2 ple 3 ple 4 ple 5 Thickness of the μm25 25 25 25 polyurethane film Thickness of the μm 30 25 45 60 adhesivefilm WVP_(pressure-sensitive) g · m⁻² · 70300 58300 65200 40300_(adhesive film, inverted cup) 24 h⁻¹ Adhesive strength N/25 mm 4.8 5.25.5 5.8 AFERA 4001 Adhesive strength N/25 mm 5.2 4.9 6.5 4.8polyurethane skin model subjective evalu- ation, normed at a standard of100% dry % 109 115 115 120 moist % 180 120 222 140 wet % 253 190 302 195

What is claimed is:
 1. A medicinal pressure-sensitive adhesive whichadheres to both dry and wet skin comprising a mixture of: (a) 20 to 50wt-% of a hydrophilic (meth)acrylate copolymer containing tertiary aminogroups; (b) 20 to 50 wt-% of a hydrophobic (meth)acrylate copolymercontaining carboxyl groups; (c) 10 to 40 wt-% of one or more mono- ordi-carboxylic acids; (d) 0 to 10 wt-% of a polyol; and (e) 0.02 to 0.5wt-% of a cross-linking agent reacting with at least one copolymer,whereby the sum of components a to e equals 100 wt-%, with a water-vaporpermeability of greater than or equal to 30,000 g·m⁻²·24 h⁻¹, measuredon a pressure-sensitive adhesive film with a thickness of 40 μm.
 2. Themedicinal pressure-sensitive adhesive of claim 1 wherein the hydrophiliccopolymer contains dimethylaminoethyl groups.
 3. The medicinalpressure-sensitive adhesive of claim 1 wherein the hydrophobic copolymercontains n-butyl acetate monomer units.
 4. The medicinalpressure-sensitive adhesive of claim 1 wherein the number of C-atoms inthe dicarboxylic acids is an even number and lies between 12 and
 16. 5.The medicinal pressure-sensitive adhesive of claim 1 wherein the numberof C-atoms in the dicarboxylic acids is an even number and lies between6 and
 10. 6. The medicinal pressure-sensitive adhesive of claim 1wherein the cross-linking agent is a metal chelate, a metal acid ester,a blocked polyisocyanate, an epoxide resin, an aziridine resin or atriazine resin.
 7. The medicinal pressure-sensitive adhesive of claim 1wherein the polyol is glycerin.
 8. A medicinal plaster with good skinadhesion comprising a pressure-sensitive adhesive of claim
 1. 9. Themedicinal plaster of claim 8 further comprising textile sheet materials,films, foams or paper as carrier materials.
 10. The medicinal plaster ofclaim 9 in sterilized form.
 11. A wound plaster comprising the medicinalplaster of claim
 8. 12. A securing plaster comprising the medicinalplaster of claim
 8. 13. An occlusive dressing for the transdermalapplication of active substances comprising the medicinal plaster ofclaim
 8. 14. The medicinal plaster of claim 8 in sterilized form.
 15. Amethod of making an occlusive dressing which is insensitive to wetnesscomprising including the medicinal pressure-sensitive adhesive of claim1 in the occlusive dressing.